From Original Ferrocene-Based Small-Molecule Design to Multifunctional Supramolecular Bactericides: Their Efficient Applications in Controlling Biofilm-Associated Bacterial Infections

Conventional bactericides struggle with biofilm barriers and inefficient deposition on hydrophobic leaves, resulting in undesirable control of plant bacterial diseases. To overcome these challenges, an innovative ferrocene-based small-molecule (FccA8R) is conceived, featuring biofilm disruption capabilities. Further optimizing FccA8R with seven-membered oligosaccharide-involved host–guest supramolecular strategy creates two kinds of biocompatible multifunctional supramolecular nanospheres (FccA8R@β-CD and FccA8R@HP-β-CD). This manipulation efficiently eradicates mature biofilm barriers while enhancing droplet retention on hydrophobic leaves. At a concentration of 56.64 µg mL⁻¹, the two materials remove Xanthomonas-biofilms by 76.32–76.83%, notably surpassing that of single FccA8R (57.96%). Their versatility extends to the enhanced inhibition of bacterial motility, extracellular enzymes secretion, and exopolysaccharides production, all reducing the bacterial virulence. In vivo pot experiments, FccA8R@β-CD and FccA8R@HP-β-CD demonstrate workable control efficacies of 48.91–52.03% against rice bacterial blight at 200 µg mL⁻¹, superior to the commercial thiodiazole-copper-20%SC (36.42%) and FccA8R-0.1%Tween (39.54%). Furthermore, these supramolecular assemblies disclose broad-spectrum bactericidal efficacy (71.45–73.19%) against kiwifruit canker, significantly higher than thiodiazole-copper-20%SC (43.05%) and FccA8R-0.1%Tween (57.24%). Besides, supramolecular bactericides are safe for plants and non-target organisms like zebrafish and earthworms. Briefly, this research builds a key foundation for creating green bactericides from small-molecule conception to eco-friendly supramolecular assemblies, realizing the prevention of bacterial diseases and environmental safety.